A vaccine for HIV is a global health priority. Efforts to develop a successful HIV vaccine using standard immune responses have so far failed. Lateral thinking is required to explore novel phenomena in HIV-specific immunity. The cytotoxic capacity of natural killer (NK) cells provides one such opportunity to open up a new horizon that could eventually be utilised in rational vaccine design. Antibody dependent cell mediated cytotoxicity (ADCC) allows for antigen-specific targeting of NK cell activity. Previous studies of the role of ADCC activity in HIV infection have been hampered by difficulties identifying and mapping these responses. We developed a novel technique to detected HIV peptide-specific antibody dependent cell mediated cytotoxicity (ADCC) mediated by NK cells in HIV positive individuals. The technique allows for rapid detection and quantification of cytokine expression by NK-cells mediated through ADCC on small volumes of blood or plasma;it also allows for mapping precise epitopes targeted by these responses. We now wish to exploit this technology to determine the biological significance of HIV-specific ADCC responses and use this knowledge to develop potentially effective HIV vaccines. PUBLIC HEALTH RELEVANCE: Novel approaches are required to determine how best to induce immunity to HIV. HIV is causing a devastating pandemic and it is widely believed that a vaccine will be essential to ultimately slowing this pandemic. This project is studying a novel immune response called ADCC which we believe may be a useful component of immunity to HIV.